Mosaic Down syndrome (mosaicism)

Mosaic Down syndrome is a rare Down syndrome variant that involves a genetic condition known as mosaicism. Mosaicism occurs when an individual who developed from a fertilized egg has two or more genetic populations of cells with different genotypes. Whereas people with the more common trisomy 21 form of Down syndrome have an extra chromosome in every cell, those with mosaic Down syndrome have a mixture of cells. In many cases, individuals with mosaic Down syndrome have some cells with the typical forty-six chromosomes and some with an extra copy of chromosome twenty-one. Some cells may even have a third copy of chromosome twenty-one. Mosaic Down syndrome typically accounts for only about 2 percent of all Down syndrome cases. While the symptoms of mosaic Down syndrome are similar to those associated with trisomy 21 Down syndrome, the presence of at least some normal cells means that the presentation of these symptoms is usually less severe.

Background

Down’s syndrome is a genetic condition that occurs when an individual has an extra chromosome in all or some of their cells. In each of the body’s cells, genetic material is stored in genes that are grouped into a series of rod-like structures called chromosomes. Under normal circumstances, the genes found within the nucleus of each cell contain twenty-three pairs of chromosomes. Those with Down syndrome have a full or partial extra copy of chromosome twenty-one in at least some of their cells. The presence of this excess genetic material has a direct impact on development that ultimately leads to the characteristics typically associated with Down syndrome. Some of these characteristics include a flattened face, upwardly slanted almond-shaped eyes, a short neck, small ears, a tongue that sticks out of the mouth, small hands and feet, tiny white spots on the iris, a palmar crease, small and sometimes curved pinky fingers, poor muscle tone, loose joints, and short height. Some people with Down syndrome may also have delayed development or behavioral problems. Many have a lower than average IQ as well.

Although Down syndrome has likely existed throughout human history, the condition was not adequately documented until the late nineteenth century. In 1866, English physician John Langdon Down published the first accurate description of what later came to be known as Down syndrome. While other scientists previously identified the common characteristics of the condition, Down was the first to describe the syndrome as a distinct phenomenon. Further research conducted over the years has shown that Down syndrome is the world’s most common chromosomal condition. According to the Centers for Disease Control and Prevention (CDC), Down syndrome occurs in roughly one in every 700 babies born in the United States.

There are three distinct forms of Down syndrome. The most common is trisomy 21, which occurs when all of a person’s cells have an extra chromosome. Translocation Down syndrome occurs when a whole or partial extra chromosome twenty-one is present, but is translocated to a different chromosome instead of being a separate chromosome twenty-one. The third form is mosaic Down syndrome.

Overview

Mosaic Down syndrome is a rare genetic condition that is different from other forms. It differs from trisomy 21 and translocation Down syndrome primarily in that it involves two distinct cell groups. Whereas the other forms of Down syndrome affect all the cells in one way or another, mosaic Down syndrome affects only some cells. This means that while some cells have the typical forty-six chromosomes, others have an extra copy of chromosome twenty-one so that they have a total of forty-seven chromosomes.

Scientists believe there are two possible explanations of how and why mosaic Down syndrome occurs. Both theories are tied to errors thought to occur during the chromosome replication and separation process that begins when an egg cell is fertilized by a sperm cell. At the moment of conception, a single cell with forty-six chromosomes is usually created. From there, the chromosomes are copied, the copies are separated, and the original cell divides to form a pair of daughter cells. As this sequence continues, the two daughter cells soon multiply into many more cells. When this process plays out without disruption, all the new cells formed will have forty-six chromosomes. However, the introduction of errors can lead to chromosomal conditions like Down syndrome. Research suggests that mosaic Down syndrome most likely occurs when an extra copy of chromosome twenty-one is present in the egg or sperm cell at conception. This results in an error in the chromosome replication and separation process leading the extra chromosome to be passed on to only one of the daughter cells. This results in the creation of one cell grouping with forty-seven chromosomes and another with forty-six chromosomes. In this explanation, the ratio of affected cells to unaffected cells would be determined based on when in the replication and separation process the error occurred. The other explanation suggests that children with mosaic Down syndrome inherit a total of forty-six chromosomes at conception, but end up having some cells with forty-seven chromosomes because of an error in the replication and separation process occurring in the early stages of development of the fetus.

Mosaic Down syndrome can be diagnosed before or after birth. Prenatal diagnosis requires the use of tests like chorionic villus sampling and amniocentesis. Through these tests, doctors can analyze chromosomes found in samples taken from tissues in the uterus. After birth, a chromosome study can be conducted using a blood sample. In either case, doctors examine the baby’s cells to determine how many chromosomes they contain. Mosaicism is typically expressed as a percentage. Most chromosome studies look at a group of twenty different cells. Diagnosis is confirmed if at least five of the twenty cells have forty-six chromosomes and the remainder have forty-seven. In this example, the baby in question would be said to have a mosaicism level of seventy-five percent because fifteen out of the twenty tested cells had an extra chromosome.

The symptoms of mosaic Down syndrome are essentially the same as those associated with trisomy 21 and translocation Down syndrome. Because individuals with mosaic Down syndrome have a varying number of cells with the typical forty-six chromosomes in addition to some with forty-seven, the characteristic symptoms are often less pronounced.

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